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Radcliffe, Naomi, Barlow, Roger, Cywinski, Robert and Beasley, P.
Development of lowenergy accelerator­based production of medical isotopes
Original Citation
Radcliffe, Naomi, Barlow, Roger, Cywinski, Robert and Beasley, P. (2013) Development of lowenergy accelerator­based production of medical isotopes. In: Proceedings of the NA ­ PAC 2013 Conference. JACoW, Geneva, pp. 1131­1133. ISBN 978­3­95450­138­0 This version is available at http://eprints.hud.ac.uk/20398/
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Proceedings of PAC2013, Pasadena, CA USA
THOBB2
DEVELOPMENT OF LOW ENERGY ACCELERATOR-BASED
PRODUCTION OF MEDICAL ISOTOPES
N. Ratcliffe∗ , R. Barlow, R. Cywinski, University of Huddersfield, Huddersfield, HD1 3BH, UK
P. Beasley, Siemens AG, Oxford, OX1 2EP, UK
Abstract
LOW ENERGY ISOTOPE PRODUCTION
INTRODUCTION
Currently the production of medical tracer isotopes for
use in imaging techniques such as SPECT (Single Photon Emission Computed Tomography) and PET (Positron
Emission Tomography) [1] relies principally upon an ageing fleet of nuclear reactors. For example the most common medical isotope 99m Tc, used in over 80% of all radiopharmaceutical procedures, is currently produced, via its
generator 99 Mo, by nuclear research reactors such as NRUCanada and HFR-The Netherlands, which together produce
over 60% of the worlds 99 Mo/99m Tc supply. Both of these
reactors are old (>50yrs) and close to decommissioning,
and while several projects are looking at other production
routes for this isotope, as yet there is no real replacement in
place [2, 3]. As these reactors near their decommissioning,
currently set at 2014-2016, there is considerable concern
that we will soon be facing a similar situation to that of the
2010 isotope crisis, when both reactors were offline simultaneously resulting in a significant decrease in the supply of
99m
Tc and the postponing or cancelation of many vital radioisotope procedures [1–5]. Due to 99m Tc monopolising
the medical isotope market little work was done developing other isotopes and many potential isotopes fell by the
wayside. The aim of this work is to resurrect some of these
isotopes as alternatives to 99m Tc as we head into another
shortage in the hope of preventing another crisis. There are
several short lived SPECT and PET isotopes that have the
potential to take some of the workload from 99m Tc.
∗ [email protected]
08 Medical Accelerators and Applications
U01 - Medical Applications
We believe that the solution to this impending problem
could lie in accelerator-based production methods, of both
99m
Tc and possible replacement isotopes. A collaboration
with Siemens is focusing on the potential of a compact,
low energy proton device for the generation of radioisotopes [6]. Such a machine could provide many more localised isotope production centres and allow for the use
of isotopes with shorter halflives. A study of optimal target designs for such a system has been undertaken using
GEANT4 simulations of low energy (<10MeV) proton induced reactions.
113M
INDIUM
113m
In is a metastable radioactive isotope that decays via
a 392 keV γ into stable 113 In with a half life of 1.7hours [7].
In 1965 it was first proposed for use as an alternative medical tracer isotope to 99m Tc for SPECT imaging in several applications such as brain and lung scanning. Trials of this isotope showed it to give results comparable to
99m
Tc images [7]. 113m In showed several advantages over
99m
Tc such in terms of chemical properties. A successful generator production system for In was developed using
113
Sn [7, 8].
Generator Production
There are several advantages of a longer lived generator system, such as the Sn/In system. The longer gap between parent half life and daughter half life makes it easier
to separate the two nuclei. It also increases the longevity of
the system for example the Sn/In(parent half life approximately 118 days) system only needs replacing once every 6 months where as the Mo/Tc(parent half life approximately 3 days) system needs replacing weekly. However
due the plentiful and cheap supply of Tc at the time very
little serious work was carried forward with this isotope.
The simplicity of the generator production system and the
advantages available from such a system has prompted the
exploration of a low energy method of production for this
generator using the reaction:
113
In(p,n)113 Sn → 113m In → 113 In
Preliminary simulation results from the TALYS data libraries show that such a reaction at 10 MeV gives a production cross section of 570mb. Further GEANT4 simulations
have been used to study target designs and feasibility of this
reaction using a <10MeV proton beam. In terms of daughter yield the most appropriate target thickness is that of just
ISBN 978-3-95450-138-0
1131
c 2013 CC-BY-3.0 and by the respective authors
Copyright Here we present methods for production of new and existing isotopes for SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) imaging using accelerator-based systems. Such isotopes are already widely used in medical diagnostics and
research, and there is constant development of new drugs
and isotopes. However the main production method for
99m
Tc, is currently in research reactors and is at risk due
to scheduled and unscheduled shut downs. Therefore, a
low cost an alternative accelerator-based system could provide many advantages. Various compact low energy proton
machines are being proposed to enable cheap and accessible production: here we present a discussion of potential
new SPECT isotopes and simulations of suitable targets for
their manufacture.
THOBB2
Proceedings of PAC2013, Pasadena, CA USA
over the stopping distance, which from these simulations
is given to be approximately 0.5mm. The generator and
daughter activity for this reaction after a 30min irradiation
of the target can be seen in Fig. 1.
Figure 2: Activity of 113 In produced from the direct reaction.
Figure 1: Activity of parent 113 Sn and daughter 133m In produced from the generator reaction.
The lifetime of a typical Sn/In generator system is 36 months [9]. The activity for this time after irradiation
can be seen in Fig. 1. Even after this time this small sample generator is producing an activity of 0.9 mCi which
in comparison to a typical single dose of microcuries per
gram [10], shows the potential of a low energy accelerator
based system for the generator production of 113m In.
c 2013 CC-BY-3.0 and by the respective authors
Copyright Direct Production
Direct production of 113m In appears to be less common
due to the short halflife of the isotope and the lack of local facilities in which to produce it. However with the introduction of our proposed system it should be possible to
make this a much more feasible production route. Both the
TENDL and EXFOR libraries can be seen to agree that a
cross section of just over 200mb can be obtained for the
following reaction:
113
Cd(p,n)113m In
for a proton beam between 9 and 10 MeV. The corresponding activity of In for a 0.5mm thick target after a
30min irradiation can be seen in Fig. 2.
The activity obtained for direct production is significantly larger than that of generator production. Such activity should be enough to service the needs for a local facility as is the proposed purpose of a low energy isotope
production system.
87M
STRONTIUM
Strontium 87m is a metastable radioactive isotope that
decays via a 388keV γ into stable 87 Sr with a half life of
2.8hours [11]. Several different strontium isotopes have
an application in nuclear medicine as due to the similar
ISBN 978-3-95450-138-0
1132
chemistry to calcium it is readily taken up in bone. There
are some isotopes such as 90 Sr which are undesirable for
medial use as replace calcium in the bone and are toxic.
Others however such as 87m Sr can be used in both diagnostic and therapeutic techniques for various skeletal diseases [11–14].
Generator Production
87m
Sr is produced primarily using the 87 Y/87m Sr generator. Literature shows many different possible methods of
producing this generator. However these are all at higher
energies ( >20 MeV). This work is focusing on low energy
techniques e.g. reactions such as
87
Sr(p,n)87 Y → 87m Sr → 87 Sr
According to the TALYS/EXFOR libraries this reaction has a cross section of approximately 600mb at 10
MeV. Further study of target design were carried out using
GEANT4 to obtain a suitable target that provides a viable
yield for medical applications. The activity obtained from
a 0.9mm thick metal target can be seen in Fig. 3.
Activity of the generator route from our simulations is of
the order of curies whilst a diagnostic dose is of the order
of millicurie. However from previous studied such as [11]
it is apparent that this target is impractical and a compound
target such as SrCl2 would be more appropriate. This reduces the number of Sr nuclei within the target requiring a
thicker compound target to keep the activity sufficient for
the 2 week lifespan that is typical of this type of generator
system.
Direct Production
It is also proposed that direct production of 87m Sr is possible through the reaction:
87
Rb(p,n)87m Sr
which according to the EXFOR libraries has a cross section of approximately 200mb in the energy range <10MeV.
The TALYS libraries also gave a cross section of 240mb at
08 Medical Accelerators and Applications
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Proceedings of PAC2013, Pasadena, CA USA
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to optimise the low energy production routes for these isotopes in the hopes of minimising the reduction of SPECT
isotopes in the predicated crisis. We will also go on to study
the potential of using this system to manufacture potential
isotopes to be introduced for both SPECT and PET.
ACKNOWLEDGMENT
N. Ratcliffe acknowledges the receipt of a joint EPSRC/Siemens CASE studentship.
REFERENCES
[1] M. Zakzouk, The Medical Isotope Shortage: Cause, Effects
and Options, (Library of Parliament, Canada, 2009).
[2] Cyclotron Produced Radionuclides: Principles and Practice, IAEA, Technical Reports Series no.456, 2008.
Figure 3: Activity of 87m Sr produced using the 87 Y/87m Sr
generator.
[3] S. Zeisler, “Cyclotron Production of Technetium-99m,”
Workshop on Acclerator-driven Production of Medical Isotopes, Daresbury Laboratory, UK, 2011.
[4] A Review of the Supply of Molybdenum-99, the Impact of Recent Shortages and the Implications for Nuclear Medicine
Services in the UK, Administration of Radioactive Substances Advisory Committee, 2010.
[5] J. Nolen, “Current and Possible New Methods for
Acclerator-Based Production of Medical Isotopes,” XXV
International Linac Conference, 2010.
[6] P. Beasley and O. Heid, “Progress Towards a Novel Compact High Voltage Electrostatic Accelerator,” PAC’11 New
York, WEP207 (2011).
[7] J. Clements et al., “Indium 113m DIETHYLTRIAMINOPENTAXETIC Acid (DTPA): A New Radiopharmacutical For Brain Scanning,” 1968.
[8] L. Colombetti et al., “Preparation and Testing of a Sterile
Sn113-In113m Generator,” 1969.
Sr produced using the direct reac-
10MeV from which the activity of 87m Sr that is produced
after a 30min irradiation of a 0.5mm thick target can be
seen in Fig. 4.
Even with such a simple, crude design such a large activity is obtained with this reaction. With more adjustment
a suitable target could be configured so as to optimise the
activity. An isotope with such a short half life is much more
likely to be produced using the direct reaction on demand
and so any effort to minimise the production time such as
short irradiation time, from these initial results this time
could be less than 30mins.
CONCLUSION
This work has shown a first test case of the feasibility
and practicality of using a low energy proton accelerator
system as a method of producing radioisotopes in quantities suitable for medical applications. This work will go on
08 Medical Accelerators and Applications
U01 - Medical Applications
[9] N. Ramamoorthy et al., “Studies on the Preparation of
113
Sn-113m In Generators,” Isotopenpraxis Isotopes in Environmental and Health Studies, 2008.
[10] www.iem-inc.com/toolmed1.html
[11] J.F. Allen and J.J. Pinajian, “A 87m Sr Generator for Medical Applications,” International Journal of Applied Radiation and Isotopes, 1965.
[12] H.B.S. Kemp et al., “The Role of Fluorine-18 and
Strontium-87m Scintigraphy in the Management of Infective Spondylitis,” The Journal of Bone and Joint Surgery,
1973.
[13] M. Van Laere et al., “Strontium 87m Scannong of the
Sacroiliac Joints in Ankylosing Spondylitis,” Annals of the
Rheumstic Diseases, 1972.
[14] R.L. Meckelnburg, “Clinical Value of Generator Produced
87-m Strontium,” Journal of Nuclear Medicine, 1964.
[15] A.G.M. Janssen et al., “A Rapid and High-Yield Preparation
Method for 87 /87m Sr Generators Using the 88 Sr(p,2n) Reaction,” Int. J. Radiat. Appl. Instrum. Part A, Appl. Radiat.
Isot., 1986.
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c 2013 CC-BY-3.0 and by the respective authors
Copyright Figure 4: Activity of
tion.
87m